Present work involved study of the mechanisms by which Mt-MtT (the mammary tumor derived by co-implantation with the mammosomatotrophic tumor MtTW10) does not regress when ovariectomy is performed, and MT-P (the mammary tumor grown by treating transplanted animals with chronic injections of drugs like perphenazine which increase serum prolactin) always regress after ovariectomy. We have eliminated many reasonable explanations to account for the failure of regression of Mt-MtT after ovariectomy. The inhibition of regression is not due to the very high prolactin, growth hormone or glucocorticoid concentration in the blood of animals bearing MtTW10. Although 17 hydroxyprogesterone caproate does not inhibit regression, the administration of progesterone and norethindrone completely prevent ovariectomy induced regression. The inhibition is not a result of MtT stimulation of the adrenal with subsequent secretion of a steroid which prevents ovariectomy induced regression. Animals bearing Mt-MtT fail to show regression of mammary tumor when adrenalectomy is combined with ovariectomy. Our current working hypothesis is that high-dose progesterone stimulates the pituitary and/or the pituitary tumor to secrete an unidentified substance which is possibly a new hormone; this substance prevents ovariectomy induced regression. Current plans involve the development of an assay for this substance.